DNA sequencing using primer-directed, dye-based termination, reversible termination, sequence-specific single-strand DNA ligation, or other sequencing protocols known in the art typically results in obtaining the informational equivalent of a single nucleotide base from a given template sequence from each reaction cycle of sequencing chemistry. The widely used capillary-based Sanger sequencing method, for example, uses a mixture of four fluorescent dideoxy terminator nucleotides per cycle to determine which of four nucleotides occurs at a given sequence position. Sequencing reactions are typically initiated by use of a priming sequence that flanks a DNA template region of interest in a given DNA clone, with the typical restriction that a single template region is sequenced. The sequence information obtained from a single conventional read provides 2 bits of information (I) per reaction cycle (I=Σ−pi log 2 (pi), where the sum is over each possible nucleotide and pi is the a priori probability of observing any given nucleotide which is equal to 25% if all four nucleotides are equally likely a priori).